Journal of Pharmacogenomics & Pharmacoproteomics

Abstrait

Epigenetic Modifications: Are we Closer to Clinical Applicability?

Frederique Ponchel and Agata N Burska

Epigenetics encompass all inheritable, although potentially reversible changes in the genome, that do not alter the DNA code, but result from both developmentally (ensuring tissue specificity) and environmentally (resulting for exposure to many factors) driven modification of the spatial conformation of the DNA through chemical modification of the nucleotide chain itself or of the chromatin associated proteins. Epigenetic controls gene expression at a higher level than transcription, imputing on the genome an environmental signature that is heritable through cell division and reflects a life-long experience. These types of modification (particularly DNA methylation patterns) explain phenotypic differences between identical twins. As opposed to genetic mutation, these modifications are reversible and are controlled by groups of enzymes (the epigenetic machinery, DNA methyltransferases (DNMT), histone deacetylases (HDACs) and histone acetyl transferases (HATs) and many more), hence, epigenetic marks include DNA methylation, histone modification and nucleosome positioning resulting in higher structural organisation of the chromatin regulating gene expression at the level of DNA accessibility for the transcriptional machinery to bind and initiate transcription.